Abstract
In recent years, fiber-based systems have been explored in the frame of tissue engineering due to their robustness in recapitulating the architecture and mechanical properties of native tissues. Such scaffolds offer anisotropic architecture capable of reproducing the native collagen fibers' orientation and distribution. Moreover, fibrous constructs might provide a biomimetic environment for cell encapsulation and proliferation as well as influence their orientation and distribution. In this work, we combine two fiber fabrication techniques, such as electrospinning and wet-spinning, in order to obtain novel cell-laden 3D fibrous layered scaffolds which can simultaneously provide: (i) mechanical support; (ii) suitable microenvironment for 3D cell encapsulation; and (iii) loading and sustained release of growth factors for promoting the differentiation of human bone marrow-derived mesenchymal stem cells (hB-MSCs). The constructs are formed from wet-spun hydrogel fibers loaded with hB-MSCs deposited on a fibrous composite electrospun matrix made of polycaprolactone, polyamide 6, and mesoporous silica nanoparticles enriched with bone morphogenetic protein-12 (BMP-12). Morphological and mechanical characterizations of the structures were carried out, and the growth factor release was assessed. The biological response in terms of cell viability, alignment, differentiation, and extracellular matrix production was investigated. Ex vivo testing of the layered structure was performed to prove the layers' integrity when subjected to mechanical stretching in the physiological range. The results reveal that 3D layered scaffolds can be proposed as valid candidates for tendon tissue engineering.